Season 2, Episode 5: Cardiovascular Care: Testing and Treating Heart Disease in Women with Dr. Kristine Burke

Evelyne: Today we’ll be talking about cardiovascular disease, especially in women. Heart disease is the leading cause of death in women, and nearly half of adults with hypertension are women. So, we’ll be talking about why that is, talk about testing, treatment, and I’m sure we’ll learn some great clinical pearls from Dr. Burke today. Dr. Burke is an expert in the reversal and prevention of chronic diseases such as dementia, diabetes, heart attacks, and strokes. She has a special focus on mold-related illness and its connection to many conditions, including research into reversing the cognitive decline of Alzheimer’s disease and dementia. She teaches functional medicine in her role as assistant clinical professor of preventive medicine at Loma Linda University School of Medicine, it’s so cool that they’re teaching functional medicine there, and is also an educator for IFM, the Institute for Functional Medicine. She’s the founder and medical director of True Health Center for Functional Medicine in Northern California, a multidisciplinary practice that delivers personalized primary care with a proprietary data-driven wellness plan that has successfully prevented any heart attacks from occurring amongst its patients in over a decade. Amazing. So, Kristine, can you tell us a little bit more about your journey to medical school and then moving into a more integrative and functional approach?

Dr. Kristine Burke: Sure. So, I attended UCLA as an undergraduate in chemistry and then went on to attend medical school at UC Davis and did all of my training, family medicine training, my sports medicine fellowship there and then went on to practice in private practice, practiced the full scope of family medicine. I delivered babies for about 15 years and did a lot of women’s healthcare as part of that practice. And then about 15, 17 years into my career, I just started feeling like I was doing everything that I was told to do, I was following the algorithms, I was prescribing the medications, I was meeting the metrics, and I was still basically managing my patients’ decline.

And that didn’t feel right, so I started getting an itch to figure out a better way to do it. And I ended up having an opportunity to spend a little bit more time on my intellectual curiosity. And when I started diving in, I first started in the area of BHRT because I had so many women that were going out and doing bioidentical hormones. I was still saying the things I was taught to say, which was, “There’s no evidence that it’s safer.” Lots of natural things have bad side effects like rattlesnake venom and hemlock and just crazy stuff that was just all part of the conventional construct, not those last two things, those of course were mine.

But these women would come back, and they were having really good outcomes and in a lot of ways they were doing better than the women that I was managing with Premarin and Provera and those medications. And so, I started looking into it because I’d been told there was no data, so I started looking to see if that was actually still true and it wasn’t at all, and there was a lot of data to the contrary. And so, then that just started me questioning all of the doctrine that I had been taught and starting to look into what are other possible explanations. And then that led me to root cause medicine and to functional medicine. So, it was a little bit of a winding journey, but I found my way there at the end.

Evelyne: I love it, and now you’re teaching it. I’m actually curious about that. So, is it an actual class in functional medicine at Loma Linda?

Dr. Kristine Burke: Yeah, so it’s a two-week functional medicine elective that satisfies their basic science requirement for an elective. And it’s essentially the introductory course for functional medicine that we extend over a two-week period. Traditionally that’s been taught by IFM as a five-day program. So yeah, it’s been really amazing, and I’ve been doing that, gosh, for maybe seven or eight years now. So, it’s several hundred people that have had the opportunity to be exposed to functional medicine and root cause medicine over the course of that.

Evelyne: That’s so cool. And do the students then maybe go on to practice functional medicine or do you hear from them later that they were able to incorporate that maybe into still going into a traditional path?

Dr. Kristine Burke: Yes, so I don’t have a lot of contact with many of the students that have taken part in the elective, but the ones that I have had gone on to do some pretty amazing things actually in functional medicine. I know one has brought functional medicine concepts into the military and the Uniformed Services health system and others are doing other really interesting projects and bringing functional medicine in. So, it does seem to have an impact.

Evelyne: That’s so cool. That’s very inspiring and motivating to hear. Hopefully we can get it into more medical schools across the country-

Dr. Kristine Burke: I agree.

Evelyne: Even just that little bit of exposure, right?

Dr. Kristine Burke: I agree.

Evelyne: Great.

Dr. Kristine Burke: Well, another thing that we do is we have medical scribes for our practice, and they are students who have graduated from college but are doing a gap year before they apply to a health professional school, either a medical school or PA school. And seven of our nine former scribes are now in medical careers. So that’s been super amazing. We’ve got one down at UC San Diego who’s opened a club and really driving student interest in integrative and functional medicine. We have another that’s been asked to lead a new residency program that’s based around functional medicine for internal medicine residents. So, we’re really expanding the fingers of impact.

Evelyne: I love it. Amazing. Thank you for that inspiration. And for any of the practitioners listening, the more we can do this and spread the word, the better. So, let’s get into the conversation. So why is it that heart disease is the number one killer in women? What is the connection there?

Dr. Kristine Burke: Heart disease is the number one killer in both genders.

Evelyne: That’s true…

Dr. Kristine Burke: But right, so it’s not so much that women are singled out, we actually enjoy a fair level of protection from heart disease while we’re still in our reproductive years. But once we go through menopause and those estrogen levels start to decline within that decade following menopause, our heart disease risk equals and, in some cases, can surpass that of men. So, it’s not so much that we’re at increased risk, it’s that we develop that risk and because we’ve been protected, it doesn’t tend to be looked for or detected in women.

Evelyne: And is the connection with estrogen, progesterone, what is it? Why is that happening?

Dr. Kristine Burke: Well, that’s a great question. I think that that’s still up for some debate, but what the most recent research is showing is that it does look like estrogen provides a protective cardiovascular effect, especially if the hormones are started within that first decade after menopause, that seems to be when it has the most impact on both reducing cardiovascular events and then also reducing all-cause mortality. We can see as much as a 30 to 50% reduction in those two things when it starts within that window.

And it’s not that we don’t continue to get benefit if we start at a later age, but the benefit is definitely less, and in some studies we see that there may be increased risk, in other studies we see that there’s some protection, so probably it evens out that there may or may not be as much benefit if we started at a later period of time for the heart. Now for the brain that data is a little bit different. Even starting estrogen later in life can have a significant impact on cognitive function.

Evelyne: Oh, that’s really interesting. I don’t think I knew that. I have been seeing more and more, just on social media about people like, “Go to your doctor and ask about bioidentical hormone replacement.” So, I want to dive a little deeper into that. My first question is, is it just estrogen? And then within that, I know there’s estradiol and estriol, and then where does the progesterone fit in with the relation to cardiovascular health? And then a lot of women are also deficient in testosterone, is there also a link with cardiovascular disease and testosterone in women?

Dr. Kristine Burke: So, the hormone balance in general, what we do at our center is that we try to mimic something that is as close to the woman’s prime years, 30s and 40s as possible. We’re not looking to get ovulatory levels of estrogen where we’re getting up into the couple hundred range, but we do want to achieve those levels that have been shown to provide benefit. So, over a serum level of 70, probably up into the low 100 seems to be the sweet spot that we’re looking for. There may be people that disagree with that, but that’s what we do. And then because estrogen and progesterone are a yin and yang, which is critically important, if a woman still has an intact uterus, it’s still important if she’s had a hysterectomy because that progesterone counters some of the stimulatory or the proliferative effects that estrogen can have. So, we believe it’s always important to have those two hormones in balance. And then similarly for testosterone, we want to bring that up into the normal range.

The correlation between testosterone and women and heart disease, to my knowledge, is still a little tenuous. I’m not familiar with the literature that either strongly supports it or refutes it, but we bring those into that mid-range normal for women.

Evelyne: Okay. And you mentioned for cardiovascular disease, we’re not exactly sure, I know you do a lot around brain health too, so I’m curious, is the research stronger in that area for hormones?

Dr. Kristine Burke: The research is definitely strong for estrogen. It’s a little bit less robust for testosterone, probably also because it’s not readily looked at. There isn’t a lot of study that’s been done specifically on that.

Evelyne: Okay, thank you. I want to actually go back a little bit. So, I think that when women go to the doctor, we go for things like weight concerns, mood. I know a lot of people now do ask about gut health and mental health and those things, but why is it that we’re not taught to think about cardiovascular health, maybe even as practitioners or as patients? Is it that there’s just a lack of research in women? Is it that we don’t have enough cardiologists talking about this? What’s going on?

Dr. Kristine Burke: I think all of those things are contributors. I think for decades these studies were done only in men, and so the huge preponderance of data was all around men. And then the difference in the way that cardiovascular disease presents in women also presents a challenge because it’s not the classic crushing chest pain for most women, it certainly can be, but it usually is much more subtle symptoms of fatigue or shortness of breath or nausea and a little bit of sweating. It’s much, much more subtle. And generally speaking, not to swipe too broad a brush, but symptoms of those nature in women are often dismissed. And so, I think that we haven’t taken those symptoms as seriously as we should in women. And it’s also hard to draw a correlation between nausea, which can have hundreds of different causes, and specifically thinking about cardiovascular disease.

So, part of it is the awareness, like you mentioned, part of it is having that higher index of suspicion. Part of it is remembering that women don’t have zero risk of cardiovascular disease like we enjoy in our younger years, it’s never zero, but you know what I mean? We have such a low risk in our younger years that it’s not really part of the consideration. And so, then the shift occurs for us after menopause, and so that requires a shift in the clinician as well. And so that hasn’t been, until recently, I mean, you definitely hear a lot more about it in recent times, paying attention to those types of symptoms in women, but before that, we weren’t recognizing it.

Evelyne: Right. And I think me being in my late 30s, for example, I’m not thinking about heart disease in my 70s, but I probably am not, thankfully, not thinking of a lot of things because I plan on staying really healthy. When you are seeing women in your practice, do you mostly see women who are in that perimenopausal/postmenopausal timeframe?

Dr. Kristine Burke: Yeah, the majority of our patients now are in that 40s and up range, and so we’re dealing a lot more with people that are either nearing the timeframe when it becomes significantly more important to be paying attention to that or are well into that timeframe.

Evelyne: And you’re a family practice doctor, so when women come to you, do they usually come because they’re having the hot flashes and some of the symptoms associated with menopause, or do they come to you because they want to do a cardiovascular checkup?

Dr. Kristine Burke: That’s a great question. So now it’s a little of both for me, but I think when you’re looking at new patients that my colleagues, the physicians that work for me are seeing now because my practice has been full for a long time, I’ve got people that have been with me for 20 years now.

Evelyne: Amazing.

Dr. Kristine Burke: But it is really fun. It is really fun. But I think when you’re looking at people that are coming in as new patients, generally speaking, they’re looking to alleviate symptoms. There’s not a lot of people who are educated enough about cardiovascular health in women to understand that we have a good decade or two-decade runway to change the course of this disease. And that’s really what we focus on in our cardiovascular wellness program. When you said is it looking for cardiovascular wellness, usually they’re not looking for that, but when they come here, they get that and then they learn about it and then they realize that there are so many things that we can be looking at that can help us to understand when those early changes are happening that are going to lead later on to this significant increase in risk.

Evelyne: So, when your patients come in, what are the general tests that you’re running on everyone when it comes to cardiovascular health?

Dr. Kristine Burke: That’s a great question, and I’ve talked about this a lot in other lectures that I’ve given. So, we want to look beyond the conventional cholesterol panel. So, we have had so much focus on cholesterol and on plaque that develops, that starts to obstruct the blood vessels. But when we look at who the events happen to, and by events, I’m talking about heart attacks, having to have a major revascularization procedure like bypass surgery or having a stroke, things of that nature. So, when we look at that 85% of those happen with less than a 70% blockage, and most of our testing in the cardiology arena is designed to find 70% or more. So, we’re missing the majority. Only 15% actually occur because of that progressive clogging of the pipes. The rest occur because there is some plaque there, not a ton of plaque, but some plaque there that becomes inflamed, that makes it vulnerable, it ruptures, and then a clot forms in that artery and that blocks the flow of the artery. That is the huge… 85% of our events happen because of that.

So just with that in mind alone, we can start to recognize that we need to be thinking about something more than cholesterol. 70% of people who have a heart attack have a normal cholesterol level. So, we have this huge, what we call residual risk, the risk of having an event even though you’re being treated to guideline levels. And so, what fills that gap? So that’s where this testing comes in. So, beyond the conventional cholesterol profile, we want to look at an advanced lipid profile, that’s looking at the different particle sizes, the size and density of the LDL particles because small dense particles are going to penetrate the artery wall, that creates damage. That’s going to be the genesis for plaque to start forming, whereas large fluffy HDL like marshmallows bouncing around in the artery, that’s not going to cause damage. So, we’re looking at that.

So, the total LDL doesn’t matter so much as, what is the composition of that LDL? Is it thousands of tiny dense particles that fill us up to this level, or is it a few hundred big fluffy particles that fill us up to that level? Because two people with the same total LDL can have a completely different particle risk profile. So that’s the first piece of the puzzle.

Then we want to start looking at what are the measures we can use that tell us about inflammation within the artery wall because it’s that inflammation that’s going to lead to that vulnerable plaque, the plaque rupture, the clot, the heart attack, and the stroke. So, the two that we prioritize at the top one is called Lp-PLA2, that’s formed in the artery wall by cells called macrophages when they’re gobbling up that bad LDL, and that tells us about the progression of plaque and also about inflammation in the wall of the artery specifically. And then there’s another one called myeloperoxidase, or MPO, and MPO will become elevated when the little covering on the plaque starts to get thin and fragile. As that thins out, the myeloperoxidase goes up and we know that our risk of an event has gone up significantly.

Then we want to start looking at… So those are what I call the five alarm fire markers. So that’s the house is burning down, we have to do something right now, if those are abnormal. Then the next level is looking at what are the things that start to become abnormal that are the precursors, that are leading us down this path. So those are things like an ADMA, which is a measure of the capacity to produce nitric oxide, which is super important and I’m sure we’ll talk more about that. We want to look at the CRP, a high sensitivity CRP, which is an inflammation marker. That’s more of a general inflammation marker. It doesn’t tell us that that inflammation is specifically in the blood vessels, but we know when that’s elevated, the risk of a heart attack goes up by about two to three-fold. If the hsCRP is elevated and the Lp-PLA2, the artery specific one, if they’re both elevated, that risk goes up 11-fold.

So, these are really highly predictive markers that we can monitor. So those are some of the most important ones that we’re looking at. Then taking it one step further upstream, looking at oxidation, oxidation of cell membrane components because that damage to the cell membrane creates a wound, if you will, and then that’s going to be a raw spot or a sore spot that’s going to attract white blood cells to attach, that also can be the genesis for starting to make plaque. In its purest form, LDL is antimicrobial, and its anti-wound. So, it’s part of that protective mechanism, but then that cycle starts to go awry, and we accumulate too much of that in the wall of the artery when these other things are also abnormal. And then we can also look at oxidized LDL because that’s damaged LDL and that damaged LDL is going to generate more activity in the artery wall from those macrophages that’s going to create more inflammation. So, there’s a lot of pieces to that puzzle, but those are the things that we want to really make sure that we’re looking at.

Evelyne: Those are great, and I love the way that you just explained them in a way that you could easily explain them to patients as well. Do you take insurance in your practice?

Dr. Kristine Burke: So, we have a membership-based practice, and we do take insurance for the things that insurance covers, like evaluation and management in the visit or if we’re doing a procedure, for example. But our membership fee allows us to have this fantastic multidisciplinary team with dietitians and health coaches, and it allows us to offer our members a carotid scan every year so that we can monitor the development of plaque. We can also monitor the vascular aging based on the thickness of the wall of the artery, because as you get more inflammation, just like if you sprain your ankle and you have inflammation in your ankle, it pops up and it gets bigger, the same happens in the lining of the artery. If there’s chronic inflammation going in the walls of the blood vessels, then we’ll see that by thickening of those artery walls. So, we can keep tabs on things structurally in that way.

Evelyne: And the reason I asked is because some of these advanced cardiovascular tests are pretty pricey. But I was wondering, I know that Cleveland Heart Lab, which is a great lab for advanced Cardiomarkers, was acquired by Quest, but do they actually cover some of these advanced tests?

Dr. Kristine Burke: They sure do.

Evelyne: Oh, they do? Oh.

Dr. Kristine Burke: Yes, they sure do.

Evelyne: Well, that’s great news.

Dr. Kristine Burke: It’s great news. So, it really allows us to do 21st century medicine. I mean, we were doing the standard lipid panel 35 years ago when I was in medical school. There has been a huge change in what’s available, but people and doctors get comfortable with what they’re familiar with, what they’re used to, what they know how to manage, and then these new things come along and there’s just a lot of skepticism. But I’ve been doing this now for well over a decade, and you mentioned our statistics where we’ve prevented heart attacks for over a decade. And so, there’s so much knowledge now and experience in those of us who’ve been doing this for a long time that this is really effective methodology and it’s consistent with the physiology.

Evelyne: Yeah. And you mentioned that the carotids can you do once a year, what about the advanced cardiovascular testing, the lab markers? How often do you do those?

Dr. Kristine Burke: That’s a great question. So, we do that once a year as part of the annual wellness process so that we can assess where they are and then if they’re abnormal, we will monitor them throughout the year. We’ll also do not the whole entire panel, but specifically those vascular inflammatory markers, we’ll do those more closely or every three or four months in somebody that has known vascular disease, somebody who’s had a heart attack before they came to us or who’s had bypass surgery or a vascularization procedure or even just has significant plaque that’s been inflamed in the past and we want to monitor to make sure we’re controlling that.

We also, this past year, have brought in another multimodal marker test and that looks at four different markers and then runs it through an algorithm that allows them to give us a prediction of what that individual’s risk of having a major event is in the next year. So, in the lowest group, it’s divided into three groups, kind of your green, yellow, red scenario. So, in the lowest risk group, 99% of those people will have no event in a year from that test. In the middle risk group, we see about one in 15, and then in the high-risk group, it’s about one in five. So that’s another way that we can make sure that all of the things that we’re doing to manage those original markers that we talked about, that those are accomplishing the job of controlling the risk for this patient.

Evelyne: And what test is that?

Dr. Kristine Burke: Oh, I didn’t know if you wanted me to say the name.

Evelyne: Sure.

Dr. Kristine Burke: It’s Prevencio Hart CVE is the one that I like to use.

Evelyne: Cool. I’ve never heard of it, so that’s really interesting. Okay, so let’s talk a little bit about treatment. I know that you have a program that you take people through. Let’s talk about diet and lifestyle first. Diet is so controversial these days, it doesn’t need to be. I just saw this video yesterday on Instagram and it was a guy eating eggs and he pulls up a video and it says, “Don’t eat eggs.” And then he grabs oatmeal and it’s like, “Don’t eat oatmeal.” And so, if we follow all the dietary advice out there, we have nothing left to eat. So, I’m curious with some of the most, I guess controversial things, especially around cardiovascular disease, I would say are around plant-based versus not, and maybe even vegan/vegetarian diets. We know there’s research there, but also around red meat also controversial. So, I was wondering if you wanted to get into those and share your thoughts.

Dr. Kristine Burke: Yeah, I can just tell you what we do and all I can rest on is my success and my statistics, but we follow basically Michael Pollan’s rules, eat real food, mostly plants. But we are not… And kind of in the Mediterranean paleo vein. I think if I was going to characterize what we recommend most, that would probably be the best characterization. Definitely plant forward. We do not shy away from lean, organic, hopefully regeneratively farmed meats, and we have very good results using that.

I think that it’s so hard to look at the data, especially around red meat or conventionally farmed meat because those farming practices are so pro-inflammatory. And then the meat that we eat from those animals that are being fed grains and things that are creating a ton of inflammation in their bodies, the meat is full of all of those inflammatory cytokines and all of that negative cell signaling and cell communication.

And so, when we bring that into the body, I have to think that that has a significantly greater negative impact. And that does seem to be what we see. When you look at most of the studies that have been done looking at red meat or meat in general, it’s done with conventional farming. And when we do what we’re doing, we see the inflammation markers come down. So, correlation is not causation as we are all well aware, but certainly we don’t see that increased inflammatory markers correlating with that type of a dietary plan.

And then the other thing that I will say is that the general, I think the things that we can almost all agree on are get rid of processed foods, reduce sugar to as low as possible, certainly eliminating the refined sugars, the refined carbs as much as we can, lots of colorful fruits and vegetables because of all the variety of different phytochemicals that they have that all have positive, well, that have many positive beneficial effects in our physiology. Those are the things that we can all agree on.

And then whether you bring in meat or you don’t bring in meat, for me, I find it very difficult for people to be a healthy vegan. It takes a lot of effort to meet your nutrient needs with that food plan because we don’t see enough omega-threes in the blood of the people that we test when they’re following that type of a food plan. And then of course we have to robustly supplement things like magnesium and B-12. So, this is just my construct, don’t shoot me people, but my construct is that I don’t think we are designed to eat in a way that doesn’t sustain life. And the absence of having essential fatty acids, and I know about ALA and plant-based omega-threes, but we just don’t see the levels that we need for cardiovascular wellness. So, when we’re looking at it from that perspective, I think we have to open that up to at least bring in fish.

A pescatarian diet meets all of the nutritional needs that we need to meet, so it doesn’t have to be other types of meats that need to be brought in, but I think that that component is pretty essential. Or, like I said, it takes a lot of effort for people to make sure that they’re getting what they need, and most people aren’t willing to put that level of effort in.

Evelyne: Since you recommend a Mediterranean-ish diet, do you have your patients also consume a certain amount of olive oil every day?

Dr. Kristine Burke: I don’t dictate the amount of olive oil, but what we recommend includes a lot of olive oil. And I will even at times recommend to someone, “Hey, it looks like we need to bring in another tablespoon of olive oil a day into what you’re eating,” because their oleic acid levels are a little bit low or something like that that we may do, but I don’t have a specified amount that I’m recommending.

And the other thing that I was going to say when we were talking about all the different dietary options is when you look at personalized medicine, when you’re doing the type of markers that we’re doing well beyond the cardiovascular piece that we’ve talked about, what you start to see is exactly what you would expect in personalized care, that we are not all the same and the perfect diet for this person that creates an excellent panel of markers creates a disaster in this person.

And I have couples where I have had that very thing happens. So, it’s really instructive because you know exactly what they’re eating, because they’re cooking together, they’re eating together. And we did vegan for a while, and this one couple that I’m thinking of, fantastic for him, disaster for her. And then we shifted the other direction, and when they brought in more meat, not just fish, but more meat, disaster for him, fantastic for her, her pre-diabetes went away, her blood sugars look amazing. It was really, really fascinating. So, I think this idea that there’s only one way is going to be really challenging to prove because I don’t think there is only one way other than those basic core things that we talked about earlier.

Evelyne: Yeah, that’s a bummer when everyone in the household has to make their own meals.

Dr. Kristine Burke: Yeah, it’s a bummer. I mean, we’ve been very creative about figuring out how to find a middle ground where they can eat together. But yeah, usually they do have to have different proteins, because her numbers just don’t look good if she doesn’t get red meat at least a couple of times a week. It’s really been fascinating.

Evelyne: And to determine that, are you using genetic testing?

Dr. Kristine Burke: No, I didn’t use genetic testing in them. It was literally just following the array of markers that we’re looking at around the cardiovascular stuff, some of which we’ve talked about, around blood sugar metabolism and the insulin resistance markers, some of the pancreatic effort markers and looking at the renal function and not just in the conventional way with a serum creatinine, but also looking at the inflammatory renal marker, which is cystatin C, which a lot of docs don’t know that The National Kidney Foundation this past year now recommends that we use the cystatin C and the creatinine together in the CKD-EPI creatinine cystatin C formula to determine renal function, the GFR, the Glomerular Filtration Rate. And so that’s now supposed to be the standard of care, but almost no one is doing it. We’ve been doing it for a long time. And it has been really interesting, you will see definite differences between what one predicts and what the other predicts, and what makes that formula nice is that it kind of brings you in the middle between the two, because they both have pros and cons.

Evelyne: What is that marker?

Dr. Kristine Burke: It’s called cystatin C.

Evelyne: cystatin C, okay. And what does it do or what does it signify?

Dr. Kristine Burke: Yeah, so it’s a measure of renal inflammation. So, it was originally utilized for monitoring kidney function in people who’d had kidney transplants because the creatinine wasn’t a sensitive enough marker in that subpopulation. And then over decades, what was found is that it was actually a very sensitive way of measuring renal function and not just in transplant patients, but because it’s an inflammatory marker, there are things that can cause it to be elevated that would make the kidney function look worse than it actually is. The kidney inflammation is bad, but maybe the kidney’s ability to do its job is not as bad as that marker would make it seem, if that makes sense?

Evelyne: Yeah. Thank you. Great clinical pearl there. Because you mentioned the Mediterranean diet, it also makes me think of the Red Wine Paradox. And I’ve mentioned on the show before, I don’t drink anymore for over four years now, we’ve had a show about gray area drinking. And I think that there is still that idea that red wine is good for us because of the resveratrol, because of the polyphenols, and that’s one of the things that makes people healthier in the blue zones. Which is interesting, though, I also see now on social media a trend toward talking about alcohol, especially in women and the detrimental effects. Can you talk a little bit about that and also just about alcohol and cardiovascular disease?

Dr. Kristine Burke: So, alcohol in and of itself, just that part, that component is something that has detrimental effects across multiple organ systems as we know. It’s detrimental for the brain, for the heart, for the liver. And I think some of what creates the disparity is that a lot of the Mediterranean diet studies have been done in and around Mediterranean countries. And the wines that are produced typically have a lower alcohol content than what we produce and consume in the US, and so I think they also tend to have a lower contamination with glyphosate. So, when we’re grappling with this with patients, and I live near the wine country, so this is a big issue for us around here. So, when people are grappling with this, I try to encourage them to make, at a minimum, let’s make some better choices about the volume of wine that we’re drinking and then where that wine is coming from, if that’s what we’re going to do. But around here, that’s a pretty tall order.

Evelyne: I have a great resource for you it’s thealcoholexperiment.com, or alcoholexperiment.com, but reading Annie Grace’s book, This Naked Mind, and then doing that was super helpful. And I think it’s a very non-judgmental approach. So might be helpful for some patients. And I feel like if somebody does that for 30 days and actually evaluates, why they drink, and just thinking more about what role alcohol plays in their lives, I feel like they can’t then unlearn that even if they go back to drinking after.

Dr. Kristine Burke: Knowledge is power, right?

Evelyne: Knowledge is power, yes. You mentioned… Actually, when you were talking about ankle swelling, you made me think of it and vessel health and the endothelial glycocalyx, and so I do want to talk a little bit about that as well today. I know we’ve covered it on other episodes. You are on the board at CalRoy, which formulates our Arterosil and Vascanox, which work on endothelial glycocalyx function as well as nitric oxide production. And so I would love to know some of your insights on using these in your own clinical practice, but I’d also love to know, first of all, because you’re so good at explaining things simply in a way that practitioners can explain it to their patients, how would you explain the endothelial glycocalyx and the importance of it and how it relates to nitric oxide production and the different pathways of nitric oxide production in the body? I know that was a long question.

Dr. Kristine Burke: No problem. So, explain it in a way that could be shared with patients more easily?

Evelyne: Yes. Yeah, okay.

Dr. Kristine Burke: So the way that I explain it to people is that within the wall of the arteries, and really it’s within the wall of the entire vascular system, so the veins, venules, arterioles, capillaries, all of them have endothelial glycocalyx, but we have this structure that’s kind of like a mat, and that mat helps to keep things away from the cells that line the artery wall. And that’s really the purpose of the endothelial glycocalyx is to create this slick non-stick layer so that the blood flows through freely, so that the white blood cells don’t want to stick to the bare patches, and, although I know we all hate Teflon, I do use the Teflon pan analogy because it’s just a great analogy for this. You know when you have a new Teflon pan, that I don’t want you using anymore, that things slide around very easily on it and when it starts to get damaged or have rough spots, bare spots, that’s where everything will stick at that spot. That’s the exact same thing that happens in your endothelial glycocalyx.

And things like high blood sugar and alcohol and high blood pressure, and in inflammatory chemical signal messengers, cytokines in your blood, those can all damage the glycocalyx. So, when we’re losing tufts of glycocalyx, those sticky spots now become where the body wants to put plaque. So, the more that we can provide the building blocks, which we do with Arterosil, then the more we can repair that layer so that it works the way that it’s supposed to work, and that helps to protect the artery from plaque and to heal the artery from plaque that’s already present.

Evelyne: How does that actually work? When you ingest that, how does it actually go to the endothelial glycocalyx?

Dr. Kristine Burke: Yeah, so the rhamnan sulfate is the building block of the proteoglycan, glycosaminoglycan structure, the fibril structure. It looks like hairs, but it’s not hairs. It’s these other fibrils. And so, when you have a structure that’s easily damaged but also resilient and very readily repaired, the more building blocks to repair it that you supply, then the easier it is for the body to recreate that glycocalyx fiber. And so that’s really how Arterosil is working in that realm.

And then of course, there’s a big feedback loop on that because the glycocalyx itself measures the wave motion of the blood in the artery and that sheer stress of motion where attached to the endothelial cells that transduces the signal into the endothelial cell to produce nitric oxide, and then the nitric oxide relaxes the vessel wall, the less constricted the vessel is, obviously the better the blood pressure is likely to be, but then also the better the flow. So, everything starts to hinge back, plus the glycocalyx houses our extracellular superoxide dismutase. So, it has a really important role in oxidation.

So now think back to what we talked about were markers that we are measuring in the cardiovascular panel, we’re looking at F2-isoprostanes or oxidized cell membrane components, those are the lipid peroxides, or we’re looking at oxidized LDL. Well, those are going to be more oxidized if you don’t have adequate antioxidant enzyme capacity. So, the endothelial glycocalyx contributes to that. Then we have our clotting factors. So clotting factors are housed within that mat or that carpet, or I like to call it a kelp forest. And so, we have von Willebrand’s factor in there, we have fibrin, fibrinogen degradation and production. So, all of these components are housed within that structure. So, anything that we can do to build it up will support those actions of the structure.

Evelyne: Kristine, I just love the way that you explain things. No, seriously-

Dr. Kristine Burke: Thank you so much.

Evelyne: … really helpful. Tell me a little bit more about the nitric oxide part. I feel like you covered how they relate to each other, but what are the different pathways of nitric oxide production?

Dr. Kristine Burke: So, we have two pathways of nitric oxide production. We have the one where we’re taking arginine, and then we’re converting that into citrulline and nitric oxide. That’s using nitric oxide synthase, so that’s our endogenous pathway because that’s our enzyme pathway. And then we have the exogenous pathway where we’re converting the nitrates or the nitrites in food into nitric oxide. And for that component, we have to have the proper type of bacteria in the oral community because those bacteria are the ones that finish off that conversion process. So, we have those two ways of making nitric oxide.

Evelyne: And I think we know about the oral microbiome and cardiovascular health connection, is that the reason that they’re connected?

Dr. Kristine Burke: No, it’s one reason that they’re connected, but it’s not the only reason that they’re connected because the other piece of it is that because the gums are so richly vascularized, there’s a lot of penetration of microbes into the vascular system. And in fact, there was a really cool study that they did at Harvard years ago now, probably in the early 2010s or maybe even before that where they aspirated the clot at the time of taking… So, somebody came into the emergency room with a heart attack, they took them to the cath lab, and then when they aspirated the clot, they analyzed those clots. And what they found was 70% of them contained bacteria from the mouth, 70%.

So, we have this component as well, and it makes sense if you think about it, because if you have an imbalance in the microbiome in the mouth and you have gingivitis, even if it’s subclinical, you don’t see red gums, but it’s happening down beneath the surface, then you have inflammation. Inflammation damages the endothelial glycocalyx, that makes it leaky. Now the bacteria can get across. And if there’s an inflamed artery within the coronary arteries, then it can lodge there, land there, create more inflammation, and then that leads to the plaque rupture.

Evelyne: Interesting, interesting. Thank you for sharing that. I’d love to hear more about some success stories that you’ve had, whether it’s working on nitric oxide production with blood pressure or with the Arterosil and the endothelial glycocalyx, can you share some?

Dr. Kristine Burke: Yeah, so we’ve had some really amazing success working with the endothelial glycocalyx in particular, and I’ve just been doing that piece longer. And in fact, we’ve submitted for publication a case series of patients in my practice, it was a retrospective analysis. But basically, what had happened is I had patients that were in this program, that we’ve talked about, that we’ve been working with all of our integrative interventions, their lifestyle interventions, and many of them even with prescriptions to alter their plaque progression in their carotid arteries.

Because the reason that we monitor the carotids is there’s about an 80% correlation with what’s happening here and what’s happening in the heart and brain. So, it’s a really great proxy because it’s easily accessible, it’s an inexpensive test, it’s a fantastic way to be able to get a peek into what’s going on in the arterial tree. So, I had these patients, and over time I had been able to accomplish with them on average about a 22% regression in their carotid plaque burden. And then I added Arterosil to their regimen, and when we re-measured them at the next testing, I had an average 55% reduction in their plaque burden.

Evelyne: Oh, my goodness.

Dr. Kristine Burke: It was enormous. It was enormous. And Arterosil is actually patented to regress plaque because they have a study using MRI plaque view, which is unfortunately not available clinically yet, but it is available in the research setting. And that uses MRI to look at not just the volume of plaque like we can see with a carotid ultrasound, but also at the composition of plaque. So, you can see that lipid-rich necrotic core, you can see the heterogeneous plaque from the high-risk inflamed plaque. So, using that, they had about the same improvement, about a 49/50% reduction in that lipid-rich necrotic core, which is the part that’s going to be fragile and prone to rupture. So really exciting that we were able to reproduce something similar in a clinical setting.

Evelyne: That’s incredible. It just makes me think, “Oh my gosh, every cardiologist needs to hear this. This needs to be in every hospital. How can we spread the word?” That’s really, really incredible.

Dr. Kristine Burke: I’ve been trying to spread the word for 10 years now, but yeah, I literally had an anesthesiologist friend of mine ask at New Year’s Eve, “If this is so amazing, why isn’t every cardiologist doing it? And I said, “That’s an excellent question, why aren’t they doing this?”

Evelyne: Hmm? So, do you feel like with using Arterosil, you’ve just been able to move the needle more than before basically?

Dr. Kristine Burke: Absolutely. And I think it’s because if we don’t have the building blocks to repair a structure that’s being frequently damaged, then it makes sense that it’s just going to get more and more denuded, it’s going to have a greater rate of failure. And so that potential for repair seems to have made a huge difference. The body wants to heal, we just get in the way or things that are going on in our bodies get in the way. And so, bringing this in, giving the building blocks to heal, allows it to do those processes, and I think that that’s why we see such profound impact.

Evelyne: That’s really interesting. I believe I heard you speak about macular degeneration and neuropathy somewhere. Can you share a little bit more about how you’ve seen those change in clinical practice?

Dr. Kristine Burke: Yeah, so with the neuropathy, especially small fiber neuropathy like diabetic neuropathy for example, that’s what has been studied with this. If you think about what’s happening at a microscopic level, you have the nerves that then have this little mesh net of very tiny vessels around the outside called the vasa nervorum, now I can’t remember the right term. But anyway, we have this mesh of arteries around that are arterioles, little, tiny ones. And we know that diabetes causes small vessel damage, probably in part through this entire mechanism that we’ve just been discussing through damage to the endothelial glycocalyx and then the end result of that.

Because in a really tiny vessel, maybe you’re just getting fibrosis of that vessel and you’re just losing that vessel’s ability to carry oxygenated blood entirely. So over time, that damages the health of the nerve because it’s not receiving oxygenated blood. And what we found was when we gave Arterosil in higher doses than we used for cardiovascular disease, twice the dose. So usually, we do one capsule twice a day for vascular risk, and we did two twice a day in the diabetic neuropathy study. And with that intense repair effort, we saw a statistically significant difference in pain experience for those patients and improvement in neuropathy scores. So, healing the blood vessels allowed healing, at least at some level, some healing of the nerves.

Evelyne: That’s amazing. And what about macular degeneration?

Dr. Kristine Burke: So macular degeneration, we haven’t studied yet, but I’ve had that study on the back of my mind for about three years now. It’s similar in concept that we think that part of the reason that this develops, and you see it with Drusen and the evidence of leaky vessels, and the endothelial glycocalyx is what regulates that selective permeability. And when it’s damaged, then it can’t regulate the permeability, and we have things leaking across that shouldn’t be, like we talked about with the mouth, or we see, for example, in the kidneys when we’re measuring urine microalbumin, that’s a proxy measure of endothelial health. So, if you look at it from that perspective, then it makes sense as a hypothesis that we may be able to impact either the severity or perhaps the progression of macular degeneration if we bring in a treatment that’s helping us improve the health of the arteries. But that’s speculative right now.

Evelyne: Okay. I have another question, because it runs in my family, lymphedema. So, if somebody has poor circulation and if a lot of lymphedema is related to narrowing or blockage of the veins, could that actually be helpful for lymphatic flow?

Dr. Kristine Burke: So, I think, yes, that it would potentially be helpful. And I think it for this physiologic schema reason. So, what is happening is we’re getting an increased leak of intravascular fluid into the tissue and into the interstitium. And in a healthy body that gets taken up by the lymphatics and taken back to the core of the body so that it’s recirculated. So, when we have this situation of developing lymphedema, we have leaky arteries, and then we have inadequate lymph return, so then the tissue expands. That tissue expansion now creates an external force that collapses the veins and collapses the lymph channels, the lymph vessels. So now they have less capacity to transport fluid back into the central circulation. So, if we can start on the vascular side by improving that vascular permeability, then we can reduce the loading of the interstitial fluid into the tissue, and then hopefully by using other techniques to help get lymph flowing, we can then reduce the amount of lymphedema or tissue accumulation of lymph fluid.

Evelyne: That’s with Arterosil, right?

Dr. Kristine Burke: That would be with Arterosil. I have –

Evelyne: Mm-hmm. And do you think-

Dr. Kristine Burke: I know you’re going to ask me about Vascanox?

Evelyne: Yeah. Is there a case for that as well, even if somebody doesn’t have high blood pressure?

Dr. Kristine Burke: We use Vascanox often, even in people who don’t have high blood pressure. So-

Evelyne: Tell me more about that.

Dr. Kristine Burke: To answer your first question, I don’t have firsthand knowledge of using it specifically for lymphedema, and I’d have to noodle on that a bit to see if I can come up with a physiologic mechanism that would make sense. But the thing is, Vascanox is so incredibly safe that there’s little to no risk in trying it to see if it could help that person’s circulation. So, what was the second question that you asked me?

Evelyne: You’ve said you also use Vascanox in people who don’t have high blood pressure?

Dr. Kristine Burke: Yes. So, we have anecdotal reports, many of them that it can be significantly helpful for erectile dysfunction. And so, I’ll often reach for it first there and have men try that first. And then also using it when we have low tissue perfusion. So, we work with a lot of mold-related illness and people with complex chronic disease, and so often they end up getting this, it just looks like tissue sludging. They just have poor circulatory return. And so, using it in that situation, again, similar to how we talked about using Arterosil with the lymphedema and in combination, often we will use them for this purpose, trying to recreate that normal sequence of events that would help it to clear out that excess fluid or to improve the tissue oxygenation.

Evelyne: Yeah, these are great clinical pearls. And we did talk about endothelial dysfunction with Dr. Mike Twyman as well in regard to nitric oxide production. I have so many more questions I could ask you, but we’re running out of time. So, there are some questions that we ask every guest on Conversations for Health. So, Kristine, what are your top three supplements for yourself that you love?

Dr. Kristine Burke: I only get three?

Evelyne: Okay, sure, all 20. List all 20.

Dr. Kristine Burke: What I share with my patients is I think that the core that we are pretty much all need are a high quality multi-vitamin/multi-mineral supplement, preferably one that supports our antioxidants very robustly as well, omega-threes and vitamin D. It is a rare person that I meet, and I live in northern California, which is sunny a lot, but it’s a rare person that I meet that has an optimized vitamin D level without some supplementation. So those are core.

Then it really starts to depend on what the other things are going on in the body, obviously, as it would in any type of personalized system. For me, I prioritize an antioxidant called C60 because it also has anti-aging benefits, and I like that. And I support my hormones. So not only with BHRT, but also with some supplemental hormones, with DHEA, for example. And I’m trying to picture my sea of supplements on my bathroom counter. What else would I not want someone to take away from me? I do use Arterosil, but I use it intermittently because vascular disease is not one of my issues. I have plenty of others, but that’s not one of them. So, I use it intermittently just because it feels like a good thing to do to support that because I know how important that it is. I’m probably not as regular with that as I would want patients to be. And let’s see, what else do I try to make sure that I always get? Oh, and glutathione support.

Evelyne: Awesome. And what are your top health practices that keep you resilient and balanced and ready to see patients every day?

Dr. Kristine Burke: Oh, my goodness. My crazy schedule. Eating well. Eating well is super important. We’re foodies. We love to cook. So that’s a really important part. Sharing that with friends or family, which bringing that community piece together is really important, and I think that’s an important part of staying grounded and staying real. And then the mindfulness practice. So, I do a lot of different things because I get a little squirrel and do this for a bit, do that for a bit. But I’ve done, what I rotate through is HeartMath and mindful breathing and meditation and yoga.

Evelyne: Amazing. And then last question for you is, what is something that you’ve changed your mind about through all of your years in practice?

Dr. Kristine Burke: Do we have another hour or two? Haha, oh my gosh, I feel like almost everything.

Evelyne: Wow.

Dr. Kristine Burke: Yeah, so many things. I mean, well, the first example where we began our conversation was my opinions about bioidentical hormone replacement therapy. I mean, that’s been a complete 180, my management of cardiovascular disease and getting, in every chronic disease, getting out of the waiting in line until your pre-disease becomes disease. That’s completely shifted. And then turning away from the idea that, now I’m talking about chronic disease, not acute, and acute diagnosis is super important, but in chronic disease, naming it is so much less important than figuring out how it happened and understanding the root causes and what the imbalances are in that person that allow them to continue in the path of disease or to support the development of disease and correcting those. And that’s a completely different paradigm shift than how I was trained.

Evelyne: Yeah. Thank you for sharing those, and your patients are lucky to have you. I can tell.

Dr. Kristine Burke: Thank you so much.

Evelyne: Where can practitioners find out more about you?

Dr. Kristine Burke: So, we’re at truehealthcfm.com. We’re actually building a new building, we’re moving next week, and we will be rebranding at the new location as True Health Center for Precision Medicine. So, swap a P for the F, but we still obviously will be doing functional medicine, but it just reflects the broader perspective that we have now with all the things we’re doing with the cardiovascular prevention precision, hypertension management precision, dementia reversal.

Evelyne: Amazing. Well, thank you so much for coming on the show today. You were absolutely excellent. I learned so much from you, and it was also really fun. So, thank you.

Dr. Kristine Burke: Thank you so much. Thanks so much for having me.

Evelyne: Thank you for tuning into Conversations for Health. Check out the show notes for any resources from our conversation today. Please share this podcast with your colleagues. Follow, rate or leave a review wherever you listen, and thank you for designing a well world with us.

Voiceover: This is Conversations for Health with Evelyne Lambrecht dedicated to engaging discussions with industry experts, exploring evidence-based cutting-edge research and practical tips.